Anticholium® Per Se

NCT ID: NCT03013322

Last Updated: 2018-01-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-28
• Study Completion Date: 2017-02-18

Brief Summary

Anticholium® per Se is a randomized, double-blind, placebo-controlled, monocentric trial to assess whether the CAP can be transferred from bench to bedside. In this pilot study, 20 patients with perioperative sepsis and septic shock as a result of intra-abdominal infection are enrolled. According to randomization, participants are treated with physostigmine salicylate (verum group) or 0.9% sodium chloride (placebo group) for up to 5 days. The mean Sequential Organ Failure Assessment (SOFA) score during treatment and subsequent intensive care of up to 14 days is used as surrogate outcome (primary endpoint). Secondary outcome measures include 30- and 90-day mortality. An embedded pharmacokinetics and pharmacodynamics study investigates plasma concentrations of physostigmine and its metabolite eseroline. Further analyses will contribute to the understanding of the role of various cytokines in the pathophysiology of human sepsis. A computer-generated list is used for blocked randomization.

Conditions

Shock, Septic; Sepsis; Perioperative Period

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Treatment Group

The treatment group receives an infusion of 0.04 mg/kg physostigmine salicylate with a maximum dose of 4 mg. The infusion is administered at 0.4 mg/min (= 1 mL/min = 60 mL/h). The initial dose is followed by a continuous infusion of 0.017 mg/min, i.e. 1 mg/h (= 0.042 mL/min = 2.5 mL/h) for 2-5 days, i.e. 48-120 hours (treatment phase).

Group Type: ACTIVE_COMPARATOR

Physostigmine

Intervention Type: DRUG

Placebo Group

The placebo group is treated with 0.9% sodium chloride.

Group Type: PLACEBO_COMPARATOR

Isotonic Saline

Intervention Type: DRUG

Interventions

Physostigmine

Intervention Type: DRUG

Isotonic Saline

Intervention Type: DRUG

Other Intervention Names

Anticholium

Eligibility Criteria

Inclusion Criteria

• Age 18-85 years
• APACHE II score <34
• Intra-abdominal infection

• findings of diffuse peritonitis or a circumscribed abscess
• Perioperative sepsis

• and secure evidence of infection, clinically backed up or secured microbiologically
• ≥2 of the following four criteria:

• fever ≥38.0° C or hypothermia ≤36.0° C secured by rectal intravesical or intravascular measurement
• tachycardia ≥90/min
• tachypnea ≥20/min or hyperventilation secured by arterial blood gas analysis with PaCO2 ≤4.3 kPa or 33 mmHg or mechanical artificial respiration
• leukocytosis ≥12,000/mm³ or leukopenia ≤4000/mm³ or ≥10% immature neutrophils in the differential count
• Shock (<24 h duration): necessary use of vasopressors despite adequate fluid resuscitation to keep systolic blood pressure ≥90 mmHg or mean blood pressure ≥70 mmHg
• No more than one planned and/or one emergency basis/as an emergency procedure performed since admission (no repeated revisions)
• No infaust prognosis of a primary or concomitant illness, expecting the death within the follow-up phase
• No do-not-resuscitate order
• Written informed consent of full-age patients/their legal guardian to participate [written consent (according to AMG § 40 (1) 3b)] and unable to consent adults [§ 41 (1) 2 AMG)]

Exclusion Criteria

• Known hypersensitivity to physostigmine salicylate, sodium metabisulfite, sodium EDTA, or any of the other ingredients of Anticholium®
• Known contraindications against Anticholium®: gangrene, coronary artery disease
• Known absolute contraindications against Anticholium®: myotonic dystrophy; depolarization block by depolarizing muscle relaxants; intoxication by "irreversibly acting" cholinesterase inhibitors; closed craniocerebral trauma; obstruction in the gastrointestinal tract (mechanical constipation); obstruction in the urinary tract (mechanical urinary retention)
• Known relative contraindications against Anticholium®: bronchial asthma; bradycardia; AV-conduction disturbances
• Having undergone splenectomy
• Having undergone solid organ transplantation
• Positive pregnancy test, pregnancy, and lactation
• Participation in another clinical trial, according to AMG or the follow-up phase of another study, according to AMG

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Heidelberg

OTHER

Sponsor Role: lead

Responsible Party

Johannes Zimmermann

Dr. med. Johannes B. Zimmermann, MSc

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Johannes B Zimmermann, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

University Hospital Heidelberg

Locations

University Hospital Heidelberg

Heidelberg, Baden-Wurttemberg, Germany

Countries

Germany

References

Pinder N, Zimmermann JB, Gastine S, Wurthwein G, Hempel G, Bruckner T, Hoppe-Tichy T, Weigand MA, Swoboda S. Continuous infusion of physostigmine in patients with perioperative septic shock: A pharmacokinetic/pharmacodynamic study with population pharmacokinetic modeling. Biomed Pharmacother. 2019 Oct;118:109318. doi: 10.1016/j.biopha.2019.109318. Epub 2019 Aug 6.

Reference Type: DERIVED

PMID: 31398669 (View on PubMed)

Pinder N, Bruckner T, Lehmann M, Motsch J, Brenner T, Larmann J, Knebel P, Hoppe-Tichy T, Swoboda S, Weigand MA, Hofer S, Zimmermann JB. Effect of physostigmine on recovery from septic shock following intra-abdominal infection - Results from a randomized, double-blind, placebo-controlled, monocentric pilot trial (Anticholium(R) per Se). J Crit Care. 2019 Aug;52:126-135. doi: 10.1016/j.jcrc.2019.04.012. Epub 2019 Apr 9.

Reference Type: DERIVED

PMID: 31035187 (View on PubMed)

Zimmermann JB, Pinder N, Bruckner T, Lehmann M, Motsch J, Brenner T, Hoppe-Tichy T, Swoboda S, Weigand MA, Hofer S. Adjunctive use of physostigmine salicylate (Anticholium(R)) in perioperative sepsis and septic shock: study protocol for a randomized, double-blind, placebo-controlled, monocentric trial (Anticholium(R) per Se). Trials. 2017 Nov 10;18(1):530. doi: 10.1186/s13063-017-2231-x.

Reference Type: DERIVED

PMID: 29126416 (View on PubMed)

Other Identifiers

D.10060224

Identifier Type: -

Identifier Source: org_study_id